Conceptualizing mental health difficulties among a pediatric oncology population from a traumatic stress perspective is gaining speed. Research has shown support for the development of posttraumatic stress reactions among chronically ill children and their family members. Despite this evidence, the majority of intervention studies have not incorporated key trauma-informed intervention components that have proven to be effective in symptom reduction for trauma-exposed children. Examining key aspects of both the child trauma and pediatric psychology fields have enabled researchers to meld their strengths into one comprehensive approach. This revised perspective has clinical implications for the development of prevention and intervention techniques that are more likely to yield superior outcomes. Yet, an evidence-based, trauma-informed intervention for youth has not yet been empirically examined among a pediatric oncology population. Thus, the purpose of this study was to examine the efficacy of TF-CBT intervention program for children/adolescents diagnosed with cancer and their parents. Methods: This was a prospective longitudinal study that utilized a single-subject, non-concurrent multiple baseline design to assess the efficacy of TF-CBT intervention. A sample of five youth (ages 9 to 15) and seven parents enrolled in the study; three youth and five parents completed their participation in the study. Manualized treatment consisted of six sessions lasting approximately two hours per session (including child and parent) that targeted psychoeducation, relaxation training, affective identification and expression skills, cognitive processes, coping strategies, trauma processing, and family processes. Examined constructs, including posttraumatic stress symptomatology, depression, quality of life, parenting stress, coping utilization, coping efficacy, somatization, internalizing, and externalizing symptoms, were assessed by child self-report, parent report, and parent self-report at enrollment (baseline), post-treatment, and one-, and three-month follow-up. Results: Simulation Modeling Analysis (SMA) revealed a statistically significant reduction, from baseline to intervention, for one parent’s PTSS (R = -0.711, p = .027) and another parent’s PTSS reduction approached significance (R = -0.747, p = .055). Comparatively, no significant reduction was found for child PTSS. One child showed a significant improvement in coping efficacy (R = 0.619, p = .048) as a function of the intervention, and an additional two child participants approached significance (R = 0.618, p = .055; R = 0.689, p = .094). Visual inspection of the data did reveal noteworthy reductions for some study participants in both domain specific (i.e., PTSS) and broader psychological outcomes (e.g., quality of life, somatization, internalizing and externalizing symptoms, etc.). Conclusions: These results provide some support for a trauma-informed CBT intervention for pediatric oncology patients in remission and their parents.